Katharine A Yuengling1, Nesri Padayatchi2, Allison Wolf3, Barun Mathema1, Tyler Brown4, C Robert Horsburgh5,6, Max R OʼDonnell1,2,3. 1. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY. 2. Centre for AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa. 3. Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY. 4. Infectious Disease Division, Massachusetts General Hospital, Boston, MA. 5. Department of Medicine, Boston University School of Medicine, Boston, MA. 6. Department of Epidemiology, Boston University School of Public Health, Boston, MA.
Abstract
BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of patients with XDR-TB. METHODS: Adult patients with XDR-TB were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing was performed on baseline Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions. RESULTS: One hundred five patients with XDR-TB (76.1% HIV-infected) were enrolled from August 2009 to July 2011. Among HIV-coinfected patients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated with improved mortality in HIV-coinfected patients (P = 0.05), as was TB culture conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN lineage (68%), with few single nucleotide polymorphism differences. CONCLUSIONS: Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared with previous South African XDR-TB/HIV treatment cohorts. Of note, this study was completed before the introduction of new antimycobacterial agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become available, it is important to monitor treatment to ensure that benefits seen in clinical trials are reproduced in high-burden, low-resource settings.
BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of patients with XDR-TB. METHODS: Adult patients with XDR-TB were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing was performed on baseline Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions. RESULTS: One hundred five patients with XDR-TB (76.1% HIV-infected) were enrolled from August 2009 to July 2011. Among HIV-coinfectedpatients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated with improved mortality in HIV-coinfectedpatients (P = 0.05), as was TB culture conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN lineage (68%), with few single nucleotide polymorphism differences. CONCLUSIONS: Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared with previous South African XDR-TB/HIV treatment cohorts. Of note, this study was completed before the introduction of new antimycobacterial agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become available, it is important to monitor treatment to ensure that benefits seen in clinical trials are reproduced in high-burden, low-resource settings.
Authors: K F Laserson; L E Thorpe; V Leimane; K Weyer; C D Mitnick; V Riekstina; E Zarovska; M L Rich; H S F Fraser; E Alarcón; J P Cegielski; M Grzemska; R Gupta; M Espinal Journal: Int J Tuberc Lung Dis Date: 2005-06 Impact factor: 2.373
Authors: Keertan Dheda; Karen Shean; Alimuddin Zumla; Motasim Badri; Elizabeth M Streicher; Liesl Page-Shipp; Paul Willcox; Melanie-Anne John; Gary Reubenson; Darshini Govindasamy; Michelle Wong; Xavier Padanilam; Alicia Dziwiecki; Paul D van Helden; Sweetness Siwendu; Julie Jarand; Colin N Menezes; Avril Burns; Thomas Victor; Robin Warren; Martin P Grobusch; Martie van der Walt; Charlotte Kvasnovsky Journal: Lancet Date: 2010-05-22 Impact factor: 79.321
Authors: Gunar Günther; Christoph Lange; Sofia Alexandru; Neus Altet; Korkut Avsar; Didi Bang; Raisa Barbuta; Graham Bothamley; Ana Ciobanu; Valeriu Crudu; Manfred Danilovits; Martin Dedicoat; Raquel Duarte; Gina Gualano; Heinke Kunst; Wiel de Lange; Vaira Leimane; Cecile Magis-Escurra; Anne-Marie McLaughlin; Inge Muylle; Veronika Polcová; Christina Popa; Rudolf Rumetshofer; Alena Skrahina; Varvara Solodovnikova; Victor Spinu; Simon Tiberi; Piret Viiklepp; Frank van Leth Journal: N Engl J Med Date: 2016-09-15 Impact factor: 91.245
Authors: Neel R Gandhi; Darren Weissman; Prashini Moodley; Melissa Ramathal; Inga Elson; Barry N Kreiswirth; Barun Mathema; Elena Shashkina; Richard Rothenberg; Anthony P Moll; Gerald Friedland; A Willem Sturm; N Sarita Shah Journal: J Infect Dis Date: 2012-11-19 Impact factor: 5.226
Authors: Elize Pietersen; Elisa Ignatius; Elizabeth M Streicher; Barbara Mastrapa; Xavier Padanilam; Anil Pooran; Motasim Badri; Maia Lesosky; Paul van Helden; Frederick A Sirgel; Robin Warren; Keertan Dheda Journal: Lancet Date: 2014-01-17 Impact factor: 79.321
Authors: R Johnson; R M Warren; G D van der Spuy; N C Gey van Pittius; D Theron; E M Streicher; M Bosman; G J Coetzee; P D van Helden; T C Victor Journal: Int J Tuberc Lung Dis Date: 2010-01 Impact factor: 2.373
Authors: Jason R Andrews; Neel R Gandhi; Prashini Moodley; N Sarita Shah; Louise Bohlken; Anthony P Moll; Manormoney Pillay; Gerald Friedland; A Willem Sturm Journal: J Infect Dis Date: 2008-12-01 Impact factor: 5.226
Authors: Muhammad Abubakar; Nafees Ahmad; Abdul Ghafoor; Abdullah Latif; Izaz Ahmad; Muhammad Atif; Fahad Saleem; Shereen Khan; Amjad Khan; Amer Hayat Khan Journal: Front Pharmacol Date: 2021-03-31 Impact factor: 5.810
Authors: N Padayatchi; N Bionghi; F Osman; N Naidu; N Ndjeka; I Master; J C M Brust; K Naidoo; A Ramjee; M O Donnell Journal: Int J Tuberc Lung Dis Date: 2020-10-01 Impact factor: 2.373